{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T12:53:31Z","timestamp":1777812811936,"version":"3.51.4"},"reference-count":40,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2019,9,6]],"date-time":"2019-09-06T00:00:00Z","timestamp":1567728000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R56 DE022637"],"award-info":[{"award-number":["R56 DE022637"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["U01 DE025633"],"award-info":[{"award-number":["U01 DE025633"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:p>\n                    Clinicians have the dilemma of prescribing opioid or nonopioid analgesics to chronic pain patients; however, the impact of pain on our endogenous \u00b5-opioid system and how our genetic profile (specifically catechol-O-methyltransferase [ COMT] polymorphisms) impacts its activation are currently unknown. Twelve chronic temporomandibular disorder (TMD) patients and 12 healthy controls (HCs) were scanned using positron emission tomography (PET) with [\n                    <jats:sup>11<\/jats:sup>\n                    C]carfentanil, a selective radioligand for \u00b5-opioid receptors (\u00b5ORs). The first 45 min of each PET measured the \u00b5OR nondisplaceable binding potential (BP\n                    <jats:sub>ND<\/jats:sub>\n                    ) at resting state, and the last 45 min consisted of a 20-min masseteric pain challenge with an injection of 5% hypertonic saline. Participants were also genotyped for different COMT alleles. There were no group differences in \u00b5OR BP\n                    <jats:sub>ND<\/jats:sub>\n                    at resting state (early phase). However, during the masseteric pain challenge (late phase), TMD patients exhibited significant reductions in \u00b5OR BP\n                    <jats:sub>ND<\/jats:sub>\n                    (decreased [\n                    <jats:sup>11<\/jats:sup>\n                    C]carfentanil binding) in the contralateral parahippocampus ( P = 0.002) compared to HCs. The \u00b5OR BP\n                    <jats:sub>ND<\/jats:sub>\n                    was also significantly lower in TMD patients with longer pain chronicity ( P &lt; 0.001). When considering COMT genotype and chronic pain suffering, TMD patients with the COMT\n                    <jats:sup>158<\/jats:sup>\n                    Met substitution had higher pain sensitivity and longer pain chronicity with a 5-y threshold for \u00b5OR BP\n                    <jats:sub>ND<\/jats:sub>\n                    changes to occur in the parahippocampus. Together, the TMD diagnosis, COMT\n                    <jats:sup>158<\/jats:sup>\n                    Met substitution, and pain chronicity explained 52% of \u00b5OR BP\n                    <jats:sub>ND<\/jats:sub>\n                    variance in the parahippocampus (cumulative R\n                    <jats:sup>2<\/jats:sup>\n                    = 52%, P &lt; 0.003, and HC vs. TMD Cohen\u2019s effect size d = 1.33 SD). There is strong evidence of dysregulation of our main analgesic and limbic systems in chronic TMD pain. The data also support precision medicine by helping identify TMD patients who may be more susceptible to chronic pain sensitivity and opioid dysfunction based on their genetic profile.\n                  <\/jats:p>","DOI":"10.1177\/0022034519871938","type":"journal-article","created":{"date-parts":[[2019,9,6]],"date-time":"2019-09-06T13:51:59Z","timestamp":1567777919000},"page":"1324-1331","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":23,"title":["\u00b5-Opioid Activity in Chronic TMD Pain Is Associated with COMT Polymorphism"],"prefix":"10.1177","volume":"98","author":[{"given":"T.D.","family":"Nascimento","sequence":"first","affiliation":[{"name":"Headache and Orofacial Pain Effort (H.O.P.E.), Biologic and Materials Sciences Department, University of Michigan School of Dentistry, Ann Arbor, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Yang","sequence":"additional","affiliation":[{"name":"Headache and Orofacial Pain Effort (H.O.P.E.), Biologic and Materials Sciences Department, University of Michigan School of Dentistry, Ann Arbor, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Salman","sequence":"additional","affiliation":[{"name":"Headache and Orofacial Pain Effort (H.O.P.E.), Biologic and Materials Sciences Department, University of Michigan School of Dentistry, Ann Arbor, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Jassar","sequence":"additional","affiliation":[{"name":"Headache and Orofacial Pain Effort (H.O.P.E.), Biologic and Materials Sciences Department, University of Michigan School of Dentistry, Ann Arbor, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Kaciroti","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA"},{"name":"Center for Human Growth and Development, University of Michigan, Ann Arbor, MI, USA"},{"name":"Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Bellile","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Danciu","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Koeppe","sequence":"additional","affiliation":[{"name":"PET Physics Section, Division of Nuclear Medicine, Radiology Department, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Stohler","sequence":"additional","affiliation":[{"name":"College of Dental Medicine, Columbia University, New York, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.K.","family":"Zubieta","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Health, Stony Brook University, Stony Brook, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Ellingrod","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.F.","family":"DaSilva","sequence":"additional","affiliation":[{"name":"Headache and Orofacial Pain Effort (H.O.P.E.), Biologic and Materials Sciences Department, University of Michigan School of Dentistry, Ann Arbor, MI, USA"},{"name":"Center for Human Growth and Development, University of Michigan, Ann Arbor, MI, 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